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Researchers Learn More About a Rare Genetic Mutation Linked to Breast Cancer

Article date:
August 8, 2014

By Stacy Simon

An international team of researchers has found that abnormal changes (mutations) to a gene called PALB2 increase the risk of breast cancer much more than previously thought. According to the study published in the August 7, 2014 issue of the New England Journal of Medicine, women with this gene mutation have a risk anywhere from 5 times to 9 times as high as women in the general population. The mutation was previously thought to raise risk by about 2 to 4 times.

Like the BRCA1 gene, the normal PALB2 gene works with the BRCA2 gene to help prevent cancer by making proteins that keep the cells from growing abnormally. Inheriting a mutated form of any of these genes raises the risk a woman will develop breast cancer during her lifetime. Mutations to the PALB2 gene are much rarer than mutations to the BRCA1 or BRCA2 genes. According to the study’s authors, only about 1% of breast cancer patients have a PALB2 gene mutation.

Varying risk

The researchers calculated the risk by studying 362 members of 154 families with PALB2 mutations. Of the participants, 311 were women, 229 of whom had breast cancer. The other 51 were men, 7 of whom had breast cancer. The risk of male breast cancer was about 8 times greater in those with PALB mutations than those in the general population, but the small number of men in the study means that these results may be due to chance. PALB2 mutations may also be linked to an increased risk of ovarian cancer, but again this finding may be due to chance because of the small number of women affected.

For women, the increased risk factor for breast cancer varied depending on age and family history. Participants younger than 40 had a breast cancer risk 8 to 9 times as high as women in the general population. Those between ages 40 and 60 had a risk 6 to 8 times as high, and those older than 60 had a risk 5 times as high.

Calculating the risk another way showed that women with no family history of breast cancer who had the PALB2 mutation had a 1 in 3 chance (about 33%) of developing breast cancer by age 70. Those with 2 or more first degree relatives (mother, sister, or daughter) diagnosed with breast cancer at a young age (by age 50) had a 58% chance of developing breast cancer by age 70.

Genetic testing

Deciding whether to have genetic testing for mutations that raise the risk of breast cancer can be complicated. In most cases, breast cancer that runs in families is not due to inherited gene mutations. Testing for these mutations can be expensive and may not be covered by insurance.

If you are considering genetic testing:

Talk to a genetic counselor, nurse, or doctor to learn about what genetic testing can and can't tell you.